Redirection of doublecortin-positive cell migration by over-expression of the chemokines MCP-1, MIP-1伪 and GRO-伪 in the adult rat brain

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• 作者：S.K. Tang ; R.A. Knobloch ; C. Maucksch ; B. Connor
• 关键词：AAV ; adeno-associated viral ; AP ; anterior posterior ; CCL ; chemokine (c-c motif) ligand ; CCR ; chemokine (c-c motif) receptor ; CldU ; 5-chloro-2-deoxyuridine ; CXCL ; chemokine (c-x-c motif) ligand ; CXCR ; chemokine (c-x-c motif) receptor ; DAB ; 3 ; 3&prime ; diaminobenzidine ; Dcx ; doublecortin ; DV ; dorsal ventral ; IdU ; 5&prime ; -iodo-2&prime ; -deoxyuridine ; GFP ; green fluorescent protein ; GRO-伪 ; growth regulatory protein-伪 ; HA ; human agglutinin ; MAP2 ; microtubule associated protein-2 ; MCP-1 ; monocyte che
• 刊名：Neuroscience
• 出版年：28 February, 2014
• 年：2014
• 卷：260
• 期：Complete
• 页码：240-248
• 全文大小：1436 K

文摘

Inflammation-induced chemoattraction plays a major role in adult subventricular zone (SVZ)-derived precursor cell migration following neural cell loss, in particular through the release of chemokines by activated microglia and macrophages. We previously demonstrated that monocyte chemotactic protein-1 (MCP-1) (chemokine (c-c motif) ligand (CCL)2), macrophage inflammatory protein-1伪 (MIP-1伪) (CCL3) and growth regulatory protein-伪 (GRO-伪) (chemokine (c-x-c motif) ligand (CXCL)1) are up-regulated following neural cell loss in the adult striatum and act as potent chemoattractants for SVZ-derived precursor cells in vitro. Based on these observations, the current study aimed to examine the individual effect of MCP-1, MIP-1伪 and GRO-伪 on the migration of adult SVZ-derived neural precursor cells in vivo. To address this without the confounding effects of injury-induced chemotactic cues, adeno-associated viral (AAV)₂-mediated in vivo gene transfer was used to ectopically express either MCP-1, MIP-1伪 or GRO-伪, or the control red fluorescent protein (RFP) in the normal adult rat striatum. The extent of doublecortin (Dcx)-positive cell recruitment from the SVZ into the striatal parenchyma was then determined at 4 and 8 weeks following AAV₂ injection. Ectopic expression either of MCP-1 or MIP-1伪 in the normal adult rat brain significantly increased the number of Dcx-positive cells and the extent of their migration into the striatum at both 4 and 8 weeks after vector injection but did not promote either precursor cell proliferation or neural differentiation. In contrast, while over-expression of GRO-伪 4 weeks after vector injection induced a significant increase in Dcx-positive cell migration compared to control, this effect was reduced to control levels by 8 weeks post injection. Further, direct comparison between MCP-1, MIP-1伪 and GRO-伪 at both 4 and 8 weeks post vector injection indicated that GRO-伪 may have a reduced effect in inducing Dcx-positive cell migration when compared to MCP-1. Combined, these results confirm that over-expression of the chemokines MCP-1, MIP-1伪 and GRO-伪 can override cues directing precursor cell migration along the rostral migratory stream (RMS) and provides a mechanism by which neural precursor cell migration can be redirected into a non-neurogenic region. Differences in the migratory effect observed between individual chemokine may be due to ligand-binding affinity and/or receptor expression on SVZ-derived precursor cells.